Left ventricular systolic dysfunction predicts long-term major microvascular complication outcomes in type 1 diabetes. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood onset diabetes
Introduction
Although cardiovascular complications due to diabetes are primarily related to atherosclerotic coronary artery disease (CAD),1 diabetes has been documented as a strong predictor of heart failure independent of ischemic heart disease and other established risk factors.2, 3 This observation has been attributed to diabetic cardiomyopathy, a complicated pathophysiological process that is characterized by the presence of abnormal myocardial performance in the absence of CAD, hypertension or valvular disease.4, 5 The underlying mechanism of compromised cardiac function in diabetes is still unclear, while accumulating evidence suggests a close link with microvascular damage due to hyperglycemia and other metabolic defects.6, 7 Indeed, microvascular complications have been consistently observed to be associated with clinical or subclinical myocardial dysfunction.8., 9., 10., 11., 12., 13. In the Multi-Ethnic Study of Atherosclerosis (MESA) study, a cross-sectional association was reported between diabetic retinopathy and left ventricular concentric remodeling.10 Similarly, diabetic retinopathy was associated with over a 2.5-fold greater risk of heart failure in the Atherosclerosis Risk In Communities (ARIC) study.11
Growing evidence shows that subclinical alterations in myocardial structure and function might occur in the very early phases of diabetes, especially in type 1 diabetes.14, 15 However, whether the early presence of these subclinical abnormalities leads to worse clinical outcomes is not known. Our aim was to examine the prognostic significance of asymptomatic myocardial dysfunction identified in young adults with long-standing type 1 diabetes in terms of predicting major outcomes of diabetes (MOD).
The composite endpoint of MOD, including both micro- and macrovascular complications, has been increasingly used in diabetes clinical studies.16., 17., 18. Specifically, the present study was designed to assess the longitudinal association between baseline asymptomatic left ventricular dysfunction and later MOD incidence and to explore the underling links of diabetic cardiomyopathy with large or small vessel diseases.
Section snippets
Study population
Participants in the current analysis were members of a cardiology substudy of the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study, a prospective cohort of childhood-onset type 1 diabetes that has been shown to be representative of the Allegheny County type 1 diabetes population.19 As described previously,20 there were 658 individuals enrolled in the EDC cohort at baseline between 1986 and 1988. Participants were examined at baseline and then assessed biennially over a 25-year
Results
At baseline, twenty-three (19.8%) participants were determined to have an abnormal LVEF using the radionuclide ventriculography. Of those with abnormal LVEF, twenty-two agreed to undergo exercise thallium scintigraphy; three had a perfusion defect and one was confirmed to have CAD on cardiac catheterization and was excluded from the current analysis. Among the 115 participants included in the present study, the baseline mean age and diabetes duration were 28 (range 18 to 45) and 19 (range 8 to
Discussion
The major finding of our study was that normotensive CAD-free type 1 diabetic patients with reduced baseline left ventricular systolic function had a greatly increased risk of incident MOD during a 25 year follow-up period. This association remained significant even with adjustment for multiple established risk factors for MOD and potential confounders. Importantly, the effect size for abnormal LVEF was greater for the prediction of MOD due to non-CAD events (mainly microvascular
Acknowledgments
The authors thank the staff and the participants of the EDC Study for the contributions.
Funding
Research reported in this study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health (grant R01-DK-034818) and the Rossi Memorial Fund.
Author Contributions
J.G. acquired, analyzed, and interpreted the data; drafted the manuscript; and performed the statistical analysis. R.G.M. acquired the data, edited and critically reviewed the manuscript for important intellectual content. T.C. acquired the data, edited and critically reviewed the manuscript for important intellectual content. W.P.F conceived and designed the study, acquired and interpreted the data, edited and critically reviewed the manuscript for important intellectual content. T.J.O.
Prior Presentation
Preliminary results were presented in abstract form at the 77th Scientific Sessions of the American Diabetes Association, San Diego, CA, 9–12 June 2017.
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Conflicts of Interest: No conflicts of interest relevant to this article were reported.